Instituto de Medicina Molecular, João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Innate Immunity and Inflammation, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Nat Immunol. 2020 Jul;21(7):766-776. doi: 10.1038/s41590-020-0674-9. Epub 2020 May 18.
Tissue-resident memory T (T) cells, functionally distinct from circulating memory T cells, have a critical role in protective immunity in tissues, are more efficacious when elicited after vaccination and yield more effective antitumor immunity, yet the signals that direct development of T cells are incompletely understood. Here we show that type 1 regulatory T (T) cells, which express the transcription factor T-bet, promote the generation of CD8 T cells. The absence of T-bet-expressing type 1 T cells reduces the presence of T cells in multiple tissues and increases pathogen burden upon infectious challenge. Using infection models, we show that type 1 T cells are specifically recruited to local inflammatory sites via the chemokine receptor CXCR3. Close proximity with effector CD8 T cells and T cell expression of integrin-β8 endows the bioavailability of transforming growth factor-β in the microenvironment, thereby promoting the generation of CD8 T cells.
组织驻留记忆 T（T）细胞与循环记忆 T 细胞在组织保护性免疫中具有关键作用，在接种后引发时更有效，产生更有效的抗肿瘤免疫，但指导 T 细胞发育的信号尚不完全清楚。在这里，我们表明表达转录因子 T-bet 的 1 型调节性 T（T）细胞促进 CD8 T 细胞的产生。缺乏表达 T-bet 的 1 型 T 细胞会减少多种组织中 T 细胞的存在，并在感染性挑战时增加病原体负担。使用感染模型，我们表明趋化因子受体 CXCR3 通过趋化因子受体 CXCR3 将 1 型 T 细胞特异性募集到局部炎症部位。与效应 CD8 T 细胞的近距离接触和 T 细胞表达整合素-β8 赋予了微环境中转化生长因子-β的生物利用度，从而促进了 CD8 T 细胞的产生。
